Effects of CD18 deficiency on the emigration of murine neutrophils during pneumonia. |
| |
Authors: | J P Mizgerd B H Horwitz H C Quillen M L Scott C M Doerschuk |
| |
Institution: | Physiology Program, Harvard School of Public Health, Boston, MA 02115, USA. |
| |
Abstract: | We hypothesized that CD18 deficiency would impair the ability of neutrophils to emigrate from pulmonary blood vessels during certain pneumonias. To directly compare the abilities of wild-type (WT) and CD18-deficient neutrophils to emigrate, mice with both types of leukocytes in their blood were generated by reconstituting the hemopoietic systems of lethally irradiated C57BL/6 mice with mixtures of fetal liver cells from WT and CD18-deficient mice. Percentages of CD18-deficient neutrophils in the circulating and emigrated pools were compared during experimental pneumonias. Similar percentages were observed in the blood and bronchoalveolar lavage fluid 6 or 24 h after intratracheal instillation of Streptococcus pneumoniae, demonstrating that no site on the CD18 molecule was required for either its adhesive or its signaling functions during neutrophil emigration. However, 6 h after instillation of Escherichia coli LPS or Pseudomonas aeruginosa, the percentage of CD18-deficient neutrophils in the bronchoalveolar lavage fluid was only about one-fourth of that observed in the blood. This difference persisted for at least 24 h after instillation of E. coli LPS. Thus, neutrophil emigration elicited by the Gram-negative stimuli E. coli LPS or P. aeruginosa was compromised by deficiency of CD18. These data, based on comparing WT and gene-targeted CD18-deficient neutrophils within the same animals, provide evidence for molecular pathways regulating neutrophil emigration, which could not be appreciated in previous studies with pharmacological blockade or genetic deficiency of CD18. |
| |
Keywords: | |
|
|