Inhibition of production of monocyte/macrophage-derived angiogenic activity by oxygen free-radical scavengers.

We showed previously that thiol-containing compounds inhibited the production of macrophage-mediated angiogenic activity. Since thiol-containing compounds may act on macrophages by affecting activation and inhibiting the production of oxygen free-radicals, we studied the effects of oxygen free-radical scavengers on production of angiogenic activity by elicited mouse peritoneal macrophages and lipopolysaccharide stimulated normal human monocytes. Monocyte/macrophage conditioned media were potently angiogenic when assayed in rat corneas, while conditioned media, from oxygen free-radical scavenger-treated cells were not. The inhibitory effect of oxygen free-radical scavengers was due to a direct effect on monocyte/macrophage production of angiogenic activity but was not due solely to a decrease in the production of the macrophage-derived angiogenic cytokine tumor necrosis factor-alpha. We conclude that oxygen free-radical scavengers are potent inhibitors of the production of macrophage-mediated angiogenic activity.     

Ecological cues, gestation length, and birth timing in African buffalo (Syncerus caffer)

We examined annual variation in the timing of conception andparturition in the African buffalo (Syncerus caffer) and thesynchrony of birth timing with resource cues, using 8 yearsof monthly birth, rainfall, and vegetation data, measured asNormalized Difference Vegetation Index (NDVI). Monthly birthshad the strongest significant correlations with NDVI and rainfalllevels 12 and 13 months in the past, respectively. In addition,the synchrony of current year births corresponds most stronglyto the synchrony of the previous year's NDVI distribution. Becausethe gestation period of buffalo has been estimated to be around11 months, these findings suggest that improved protein levels,occurring approximately a month after the first green flushof the wet season, are either a trigger for conception or conceptionhas evolved to be synchronous with correlated environmentalcues that ensure females enter a period of peak body conditionaround the time of conception and/or parturition. With a gestationperiod of approximately 340 days, parturition occurs to takeadvantage of the period when forage has its highest proteincontent. A comparative analysis of gestation periods withinthe subfamily Bovinae indicates that African buffalo have aprotracted gestation for their body size, which we suggest isan adaptation to their seasonal environment. We also found thatinterannual variation in the birth distribution suggests a degreeof plasticity in the date of conception, and variation in thenumber of calves born each year suggest further synchrony ata timescale longer than a single year.     

Production of collagenase by mouse peritoneal macrophages in vitro. Characterization of sites of cleavage of tropocollagen.

Macrophages from mineral oil-stimulated mice produce collagenase at a constant rate over several days in culture. Phagocytosis of latex does not increase production of enzyme. Gel electrophoretic and electron microscopic analyses indicate that the specificity of the macrophage enzyme is similar to that of other previously characterized mammalian collagenases.     

Transforming growth factor-beta (TGF beta) is chemotactic for human monocytes and induces their expression of angiogenic activity

TGF beta stimulates human blood monocyte migration, with peak migratory response occurring consistently at a concentration of 16-100 fg/ml. Checkerboard analysis revealed both chemotactic and chemokinetic components to this response. At higher concentrations (10-100 pg/ml), TGF beta stimulated expression of angiogenic activity by monocytes. While mRNA for TNF alpha was undetectable in resting monocytes, high steady state levels of TNF alpha mRNA were rapidly induced in TGF beta-treated monocytes. TGF beta is secreted by a number of neoplastic cells as well as normal cells such as platelets and lymphocytes. TGF beta may recruit monocytes from the circulation, and subsequently activate them to express angiogenic activities such as TNF alpha, thus playing an important role in wound repair, inflammation and tumor growth.