Effect of Macrolide Antibiotics on Macrophage Functions

Macrolide antibiotics have a variety of actions other than antimicrobial activities. Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effects of macrolide antibiotics on macrophage functions. For the macrophage, we used the mouse macrophage cell line J774.1. The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage. In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans. These results suggest that macrolide antibiotics stimulate macrophage functions.     

Expression of macrophage functions in hybrids of a myeloma cell line with inflammatory macrophages: Evidence for negative control mechanisms in the expression of macrophage functions

Mouse inflammatory macrophages from C57BL/6N mice were fused with BALB/c mouse-derived myeloma cells (the CANS series). The hybrids in the early period after cell fusion (8 weeks) showed no macrophage functions (chemotaxis, EA and EAC rosette-forming abilities, phagocytosis or lysozyme production). EA rosette-forming ability was observed when these hybrids were treated with trypsin, whereas other macrophage functions were not. After prolonged culture, the hybrids (12 clones of 13 randomly selected) showed all the macrophage functions along with chromosome loss. Myeloma cell functions ( light chain production) were found in the young hybrids soon after cell fusion but were absent in the aged hybrids. These results indicated that reexpression of macrophage properties, except for EA rosette-forming abilities, takes place after the loss of chromosomes or genes repressing the expression of macrophage functions.     

Effect of streptococcal pyrogenic exotoxin on rabbit macrophage functions in vitro: mediation by splenic lymphocytes

Streptococcal pyrogenic exotoxin (SPE) showed no direct effect on rabbit macrophage functions in vitro. However, when splenic lymphocytes were added to macrophage cultures, SPE caused marked augmentation of glucose consumption and superoxide anion production, and concomitant inhibition of phagocytosis without loss of cell viability. The SPE effects were demonstrated to be mediated by a soluble factor(s) released from the splenic lymphocytes in response to SPE stimulus.     

The generation of macrophage-like cell lines by transfection with SV40 origin defective DNA

Two cell lines with properties of mature macrophages have been generated by transfection with SV40 DNA mutated in the origin of replication. One line, BAM, was derived from bone marrow cells from a BALB/c mouse. The other line, BAC1, was derived from splenic adherent cells from a (BALB/c X A.CA) F1 mouse. Both lines produce lysozyme, collagenase, and esterase, bear Fc receptors, and engage in Fc-mediated phagocytosis. Both lines require colony-stimulating factor-1 for continued proliferation. In addition, they express Ia antigens, and may be induced to secrete IL 1. This technique should make possible the generation of Ia-bearing diploid macrophage lines from any strain of mouse. In addition, it may be possible to use this technique to derive monocyte lines from species in which wild-type SV40 DNA causes a lytic infection.     

Suppression of splenic macrophage Candida albicans phagocytosis following in vivo depletion of natural killer cells in immunocompetent BALB/c mice and T-cell-deficient nude mice

The resistance of mice to systemic infections caused by Candida albicans is associated with activated splenic macrophages. In addition, there is a correlation between natural killer (NK) cell activation and the resistance to systemic candidiasis. The present study was designed to clarify the role of NK cells in the control of splenic macrophage C. albicans phagocytosis by either depleting NK cells (anti-asialo GM(1) treatment) or maintaining them in an activated state (tilorone treatment) in both immunocompetent BALB/c mice and T-cell-deficient nude mice. The results of the in vitro phagocytosis assays were analyzed by flow cytometry and demonstrate the pivotal role of NK cells in controlling the capacity of splenic macrophages to phagocytose C. albicans. In summary, these data provide evidence that the NK cells are the main inducers of phagocytic activity of splenic macrophages and that they mediate the protection against C. albicans systemic infection.     

Opioid and non-opioid receptor-mediated immunoregulatory role of Leucine-enkephalin in teleost Channa punctatus

Leucine-enkephalin (Leu-enk) is an endogenous opioid peptide and highly conserved throughout the vertebrates. Despite its conserved nature, the immunoregulatory property of Leu-enk is explored only in mammals. The present study describes the immunomodulatory role of Leu-enk in a lower vertebrate, spotted murrel Channa punctatus. Leu-enk increased the percentage phagocytosis and phagocytic index, though its stimulatory effect on phagocytosis markedly decreased at concentrations higher than 10^?9 M. Moreover, it had bell-shaped stimulatory effect also on the superoxide production by phagocytes. On the other hand, Leu-enk showed bimodal effects on nitrite release. The lower concentrations of Leu-enk produced inhibitory effect, while higher concentrations had stimulatory effect on nitrite release. Interestingly, the Leu-enk-induced increase in nitrite release was unaltered by non-selective opioid receptor antagonist though the same completely antagonized the inhibitory effect of Leu-enk on nitrite release and the stimulatory effect on phagocytosis and superoxide production. This suggests that the stimulatory effect of Leu-enk on nitrite production is mediated by the non-opioid receptor. Further, δ-opioid receptor was precisely seen involved in mediating the stimulatory effect of Leu-enk on phagocytosis and superoxide production, or inhibitory effect on nitrite release. It can be concluded that Leu-enk regulates the innate immune response of splenic phagocytes acting via both opioid and non-opioid receptor in the fish C. punctatus.     

In vitro inhibition of the helper activity of GAT-specific T-cell lines by a syngeneic anti-idiotypic serum: preferential effect on the IgG response

We described in this paper the characteristics of a syngeneic anti-idiotypic serum made in BALB/c against BALB/c anti-poly (Glu⁶⁰ Ala³⁰ Tyr¹⁰) (GAT) antibodies. This serum recognizes idiotypic determinants present in all anti-GAT sera whatever the allotypic markers of the mice used to prepare the sera. The functional effect of this serum on two helper cell lines is also described. Cell line BDF₁/52 was obtained from GAT immunized lymph node cells (LNC). Cell line BDF₁/E₃ was selected from splenic T-cells educated in vitro on GAT-pulsed adherent cells. Both lines were propagated in presence of filler cells, antigen, and medium containing T-cell growth factor(s) from splenic cells activated with concanavalin A. Both cell lines exhibit a helper activity as measured by the plaque-forming cell (PFC) response they induce in vitro in the presence of DNP-GAT and DNP sensitized B cells. Their helper activity is specific and they require a hapten-carrier bridge to activate B cells. These lines are able to induce IgG₁, IgG_2a and IgG_2b anti-TNP PFC. Syngeneic anti-idiotypic serum B 658 inhibits specifically the function of these two lines but does not affect the helper activity of an OVA-specific T-cell line. The blocking activity of the serum can be adsorbed on a hybridoma protein with anti-GAT activity. This inhibition affects more dramatically the IgG₁ response than the IgG_2a and IgG_2b responses.     

Differential Suppressive Effects of Testosterone on Immune Function in Fresh Water Snake,Natrix piscator: An In Vitro Study

Reptiles represent the crucial phylogenetic group as they were the ancestors of both birds and mammals hence very important to study. The objectives of the present study were to investigate the potential roles of testosterone in the innate immune responses and splenic lymphocyte proliferation in fresh water snake, Natrix piscator. Animals were mildly anesthetized and spleens were taken out to study the splenic macrophage phagocytosis, super oxide production and nitrite release using in vitro testosterone. Splenic lymphocytes were isolated by density gradient centrifugation and were studied for mitogen induced proliferation in presence of in vitro testosterone. Testosterone suppressed the phagocytosis and nitrite release in a concentration dependent manner. Biphasic suppressive effect of testosterone was observed in superoxide production as judged by reduction of nitroblue tetrazolium salt where salt reduction was suppressed at lower and higher concentrations of testosterone. Mitogen induced splenic lymphocyte proliferation was also suppressed by testosterone. By suppressing immune responses, testosterone may, therefore, act as a physiological mechanism regulating the relative amount of energy invested into either reproductive effort or immunocompetence.     

Changes in several functions of murine peritoneal macrophages by N-acetylcysteine and thioproline ingestion. Comparative effect between two strains of mice

The administration of the thiol compounds, N-acetylcysteine (NAC) and in particular thioproline (thiazolidine-4-carboxylic acid) at 0.1% w/w concentration in the diet, improves lymphocyte functions in old female Swiss mice, as has been shown in our previous studies. In the present work, adult mice from two different strains, namely BALB/c (an inbred strain) and OF1-Swiss (noninbred strain), were fed a diet supplemented with the above dose of each thiol compound jointly for five weeks. At 28 weeks of age, peritoneal cell suspensions were obtained and different steps of the phagocytic process, the most representative activity of macrophages, as well as interleukin-1beta (IL-1beta) production, were studied. Thus, adherence to substrate, mobility directed to a chemoattractant gradient (chemotaxis), ingestion of inert particles and superoxide anion production were analysed. The results show that diet supplementation with NAC plus thioproline increased all macrophage functions studied with the exception of superoxide anion production, which was decreased. These effects were more evident in macrophages from Swiss mice, whereas in BALB/c mice the stimulation of phagocytosis and IL-1beta production was lower and no differences were seen after treatment in adherence and superoxide anion production. These data suggest that immune function can be improved in adult mice by administration of the above thiol compounds, especially in the noninbred strain of OF1-Swiss mice.     

Tyrosine Phosphorylation of Wiskott-Aldrich Syndrome Protein (WASP) by Hck Regulates Macrophage Function

We have shown previously that tyrosine phosphorylation of Wiskott-Aldrich syndrome protein (WASP) is important for diverse macrophage functions including phagocytosis, chemotaxis, podosome dynamics, and matrix degradation. However, the specific tyrosine kinase mediating WASP phosphorylation is still unclear. Here, we provide evidence that Hck, which is predominantly expressed in leukocytes, can tyrosine phosphorylate WASP and regulates WASP-mediated macrophage functions. We demonstrate that tyrosine phosphorylation of WASP in response to stimulation with CX3CL1 or via Fcγ receptor ligation were severely reduced in Hck^−/− bone marrow-derived macrophages (BMMs) or in RAW/LR5 macrophages in which Hck expression was silenced using RNA-mediated interference (Hck shRNA). Consistent with reduced WASP tyrosine phosphorylation, phagocytosis, chemotaxis, and matrix degradation are reduced in Hck^−/− BMMs or Hck shRNA cells. In particular, WASP phosphorylation was primarily mediated by the p61 isoform of Hck. Our studies also show that Hck and WASP are required for passage through a dense three-dimensional matrix and transendothelial migration, suggesting that tyrosine phosphorylation of WASP by Hck may play a role in tissue infiltration of macrophages. Consistent with a role for this pathway in invasion, WASP^−/− BMMs do not invade into tumor spheroids with the same efficiency as WT BMMs and cells expressing phospho-deficient WASP have reduced ability to promote carcinoma cell invasion. Altogether, our results indicate that tyrosine phosphorylation of WASP by Hck is required for proper macrophage functions.     

Phagocytosis Deficiency of Macrophages in NOD.H-2h4 Mice Accelerates the Severity of Iodine-Induced Autoimmune Thyroiditis

Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2^h4 mouse thyroids by comparing the sequence of events in tissue samples. We also investigated the role of macrophages by comparing macrophage phagocytosis function in BALB/c, C57BL/6, and NOD.H-2^h4 mice treated with different levels of iodine. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and thyroid inflammatory scores revealed that apoptosis (2 weeks) occurred before inflammatory infiltration (4 weeks). Phosphatidylserine (PS) expression on the extracellular surface of the cell membrane and double-stranded DNA fragments associated with apoptosis appeared at 2 and 8 weeks, respectively. Additionally, although apoptosis was enhanced in the thyroids of mice supplemented with excess iodine (0.05 ± 0.12 vs 1.63 ± 0.82% for BALB/c, 0.09 ± 0.14 vs 1.51 ± 0.34% for C57BL/6, and 0.07 ± 1.11 vs 4.72 ± 0.62% for NOD.H-2^h4 mice), only NOD.H-2^h4 mouse thyroids presented with inflammation. Furthermore, macrophages from NOD.H-2^h4 mice (44.46 ± 1.79%) exhibited decreased phagocytotic activity relative to that in BALB/c (54.21 ± 4.58%) and C57BL/6 (58.96 ± 4.04%) mice. There were no differences in phagocytosis function between NOD.H-2^h4 mice supplemented with excess iodine or left untreated (24.50 ± 2.66 vs 21.71 ± 1.79%, p = 0.06). In conclusion, deficiencies in the apoptosis clearance of macrophages in NOD.H-2^h4 mice may constitute an early pathogenic mechanism in AIT that is not influenced by iodine intake.

     

Enhancement of macrophage Fc-dependent phagocytosis by resident thymocytes: effect of a unique heat-stable lymphokine

Lymphocytes, activated by lectins or specific antigens, have been shown to enhance macrophage phagocytosis through the elaboration of a heat-labile soluble factor(s). Recent evidence from our laboratory revealed that resident (nonactivated) murine thymocytes and splenic lymphocytes increase peritoneal macrophage glucose metabolism through the elaboration of a heat-stable soluble factor(s). Therefore, we investigated the effect of resident lymphocyte subpopulations on macrophage Fc-dependent phagocytosis. Thioglycollate-elicited and resident peritoneal macrophages from BALB/c mice were cultured in serum-free media with syngeneic resident thymocytes or splenic T lymphocytes. Macrophage Fc-dependent phagocytosis was assayed by measuring the ingestion of 51CrSHEA. After 4 days in vitro, resident thymocytes produced a mean 160 (+/- 31) and 136% (+/- 22) increase in Fc-dependent phagocytosis by thioglycollate-elicited (thio-macrophages) and resident peritoneal macrophages, respectively. Splenic T lymphocytes increased thio-macrophage phagocytosis by 112% (+/- 41) under similar conditions. Macrophage Fc-dependent phagocytosis was increased after 24 hr of co-culture by supernatant derived from resident thymocytes and could be further enhanced by supernatant from Con A-activated thymocytes. Supernatant from guinea pig embryo fibroblasts did not increase macrophage phagocytosis. The soluble factor(s) was produced by resident thymocytes after 24 hr of preculture. This factor was active despite heating at 100 degrees C for 30 min whereas the effect of Con A-activated thymocyte supernatant was heat-labile. The stimulatory effect of resident thymocyte supernatant was not observed when the macrophages and supernatant were cultured in 2% FCS. In contrast to the factor(s) produced by resident thymocytes, the factor(s) in FCS that increased phagocytosis was heat-labile. These data suggest thymocytes and splenic T lymphocytes promote macrophage Fc-dependent phagocytosis in the absence of antigenic or lectin stimulation. This previously unrecognized effect of resident thymocytes is due to a unique heat-stable soluble factor(s) that is concealed in the presence of serum.     

Inflammatory and Phagocytic Response to Experimental Campylobacter jejuni Infection in Mice

After intraperitoneal inoculation with Campylobacter jejuni BALB/c, Swiss and DBA mice show a peritoneal inflammatory response of different intensity. Only BALB/c mice have a strong peritoneal response. Simultaneous intraperitoneal inoculation of C. jejuni plus FeCl₃ increase both inflammatory response and phagocytic activity in Swiss mice, without production of diarrhea. Some thermostable compounds of C. jejuni have a very strong chemotactic activity against peritoneal cells of mice, whereas a diffusible, thermolabile and glutaraldehyde-resistant factor has an inhibitory effect over murine peritoneal cell phagocytosis. Bactericidal activity of peritoneal cells increased after in vitro re-challenge with C. jejuni. Bacteremia is present in all the mice strains tested, but the clearance is quick in DBA and slow in BALB/c and Swiss mice. These experiments confirm that in mice, peritoneal non-specific mechanisms of defense, such as macrophages, play an important role in order to control C. jejuni infection.     

Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide.

Macrophages derived from MSV-induced tumors and several macrophage cell lines showed direct cytolytic activity in an 18-hr ⁵¹Cr release assay against tumor target cells. The cytolytic activity of these macrophages was augmented by the addition of muramyl dipeptide (MDP) to the cytotoxicity assay, an effect similar to that observed with bacterial lipopolysaccharide. The stimulation of macrophage-mediated cytotoxicity by MDP appeared to be under genetic control since macrophages from BALB/c mice were augmented with MDP while those from C57BL/6 animals were not. MDP appears to act directly on the macrophage without the participation of any other cell type, since MDP increased the activity of the macrophage cell lines.     

Tick saliva regulates migration, phagocytosis, and gene expression in the macrophage-like cell line, IC-21

We studied the effects of tick saliva on cell migration, cell signaling, phagocytosis, and gene expression in the murine macrophage cell line, IC-21. Saliva increased both basal- and platelet-derived growth factor (PDGF)-stimulated migration in IC-21 cells. However, saliva did not affect PDGF-stimulated extracellular signal-regulated kinase (ERK) activity. Zymosan-mediated interleukin-1 receptor associated kinase (IRAK) activity increased when cells were pretreated with saliva. Saliva suppressed phagocytosis of zymosan particles by IC-21 cells. An RT² Profiler™ PCR Array revealed that saliva regulates gene expression in a manner consistent with an immune response skewed toward a Th2 reaction, which is characterized by production of anti-inflammatory cytokines IL-4 and IL-10. Our results using IC-21 cells suggest that Dermacentor variabilis has evolved a mechanism for regulating macrophage function, which may contribute to the tick’s ability to modulate immune function.     

Time course study of H-2 and other antigen expression by hybrids of a myeloma cell line with inflammatory macrophages

The hybrids (the CANS lines) between inflammatory macrophages from C57BL/6N (B6) mice (H-2^b) and BALB/c mouse (H-2^d)-derived myeloma cell line NS1 in the early period after cell fusion showed no macrophage functions. However, most of the hybrids expressed these functions after prolonged cultivation accompanied with chromosome loss. In contrast, the hybrids initially displaying myeloma functions ( light chain production) lost this function when they exhibited macrophage functions. We studied the expression of cell-surface antigens in these hybrids and found that hybrids in the early period after cell fusion codominantly expressed both parental cell H-2 antigens (H-2K^b, H-2K^d, and H-2D^d) but not the H-2D^b antigen. On the other hand, aged hybrids strongly expressed the H-2 d antigen but lacked the H-2K^b antigen. Alternatively, these aged hybrids with macrophage functions expressed antigen(s) as detected with antiaged CANS-196 cell sera and asialo GM1 antigen, both of which were thought to be found exclusively on macrophages. Thus, the expression of cell-surface antigens in these hybrids was greatly altered after cell fusion.     

The effect of ethanol on arachidonic acid metabolism in the murine peritoneal macrophage

Exposure to ethanol in man has been linked to an alteration of the immune surveillance system and reduced ability of the macrophage to undergo phagocytosis. Since ethanol has been suggested to alter membrane function and inhibit the production of calcium ionophore stimulated synthesis of prostaglandins and leukotrienes by the human neutrophil and transformed murine mast cell, the dose response effect of ethanol on the biosynthesis of icosanoids by the peritoneal macrophage during zymosan phagocytosis was studied. Peritoneal macrophages from two inbred strains of mice derived from a common stock (HS) and selected for sensitivity to ethanol (shoprt sleep [SS]/long sleep [LS]) were studies. Zymosan phagocytosis was found to lead to synthesis of LTC₄ (70 ng/10⁶ cells), 6-keto-PGF_1a (5 ng/10⁶ (3 ng/10⁶ cells). For the HS macrophage, ethanol caused a dose dependent inhibition of these lipid mediators as well as inhibition of phagocytosis and release of beta-hexosaminidase. However, a difference was observed in arachidonate metabolism stimulated by phagocytosis between the LS and SS mice below 100 mM ethanol. The SS mouse had a 50% inhibition of cyclooxygenase products at 86 mM ethanol with no inhibition of lipoxygenase metabolites. The LS mice had a trend suggesting increased lipoxygenase metabolites below 100 mM ethanol. At these levels of ethanol which can be found in man, these results suggest there may be differential production of lipid mediators under genetic control.     

Peripheral Monocyte Functions and Activation in Patients with Quiescent Crohn’s Disease

Recent developments suggest a causal link between inflammation and impaired bacterial clearance in Crohn’s disease (CD) due to alterations of intestinal macrophages. Studies suggest that excessive inflammation is the consequence of an underlying immunodeficiency rather than the primary cause of CD pathogenesis. We characterized phenotypic and functional features of peripheral blood monocytes of patients with quiescent CD (n = 18) and healthy controls (n = 19) by analyses of cell surface molecule expression, cell adherence, migration, chemotaxis, phagocytosis, oxidative burst, and cytokine expression and secretion with or without lipopolysaccharide (LPS) priming. Peripheral blood monocytes of patients with inactive CD showed normal expression of cell surface molecules (CD14, CD16, CD116), adherence to plastic surfaces, spontaneous migration, chemotaxis towards LTB4, phagocytosis of E. coli, and production of reactive oxygen species. Interestingly, peripheral blood monocytes of CD patients secreted higher levels of IL1β (p<.05). Upon LPS priming we found a decreased release of IL10 (p<.05) and higher levels of CCL2 (p<.001) and CCL5 (p<.05). The expression and release of TNFα, IFNγ, IL4, IL6, IL8, IL13, IL17, CXCL9, and CXCL10 were not altered compared to healthy controls. Based on our phenotypic and functional studies, peripheral blood monocytes from CD patients in clinical remission were not impaired compared to healthy controls. Our results highlight that defective innate immune mechanisms in CD seems to play a role in the (inflamed) intestinal mucosa rather than in peripheral blood.     

Changes in the superoxide production and other macrophage functions could be related to the mortality of mice with endotoxin-induced oxidative stress

Free radicals and proinflammatory cytokines from phagocytes have been implicated in the pathogenesis of endotoxic shock, a disease with high mortality caused by Gram-negative bacterial endotoxin. In the present study, male BALB/c and Swiss mice received intraperitoneally lipopolysaccharide (LPS) at 100 mg/kg and 150 mg/kg, respectively, that led to a lethal endotoxic shock (100 % of mortality before 30 h). Swiss mice injected with 100 mg/kg, that did not show lethal endotoxic shock, were also studied. Peritoneal macrophages were obtained from animals at 2, 4, 12 or 24 h after injection of LPS or saline (control) solutions. Superoxide anion and tumor necrosis factor (TNFalpha) production were determined in these cells as well as other functions such as adherence capacity, chemotaxis and phagocytosis. The increase in superoxide anion production after endotoxin injection was higher in cells from mice with lethal shock than in those with non-lethal shock. However, the enhancement of TNFalpha production was similar in all cases, although in Swiss mice the highest levels of TNFalpha were observed at 1.5 h after endotoxin injection, while in BALB/c mice they occurred at 2 h after LPS injection. This oxidative stress was also revealed by the other functions analyzed, since adherence to substrate and phagocytosis were stimulated and chemotaxis was decreased after endotoxin injection as compared to controls, the differences being even more significant in animals with lethal shock. These data suggest that these changes, mainly the increased production of free radicals even more than the TNFalpha release, could be involved in mouse mortality caused by LPS.     

A quantitative and qualitative study of blood monocytes in patients with bronchogenic carcinoma

Summary Absolute circulating number and functions of blood monocytes (i.e., pinocytosis, phagocytosis, and chemotaxis) were studied in 25 patients with untreated bronchogenic carcinoma and in 28 control subjects. The absolute circulating monocyte count was increased in 20 (80%) of the patients. There was no difference in the pinocytic and phagocytic activity of patient and control monocytes. In contrast, patient monocytes showed depressed chemotactic responsiveness. This defect was more severe in small cell anaplastic carcinoma than in the other histologic types of bronchogenic carcinoma (P=0.001), and may explain the difference in macrophage infiltration seen in solid tumours of the lung. There was no correlation between chemotaxis and clinical stage. Depressed chemotaxis may be related to a plasma factor, since patient plasma inhibited the chemotaxis of control monocytes as well as the activity of chemotactic agents. The defective chemotaxis and the presence of plasma inhibitory activity may interfere with the ability of blood monocytes to accumulate as macrophages in tumour sites. Abbreviations used in this paper are: MCR, monocyte chemotactic response; SAC, small cell anaplastic bronchogenic carcinoma; OBC, non-small cell bronchogenic carcinoma MEM, Eagle's minimal essential medium; CFI, chemotactic factor inhibitor(s); HSA, human serum albumin