Role of Mac-1 (CD11b/CD18) in neutrophil functions in vivo

In previous studies we obtained evidence that Mac-1 is not necessary for peritoneal emigration of neutrophils in mice deficient in CD11b (Mac-1 -/-) or following administration of blocking antibody to CD11b (Lu et al. FASEB J., A1281, '96). LFA-1 (CD11a/CD18) on neutrophils appears to be sufficient for peritoneal emigration. In the current study we investigated the role of Mac-1 in neutrophil adhesion to fibrinogen, and degranulation in vivo. Fibrinogen-coated Mylar discs were implanted in the peritoneal cavity of Mac-1-/- or Mac-1+/+ mice, and 16 hours later discs and inflammatory exudate were harvested. While neutrophil influx was not significantly different, neutrophil adhesion to the discs was reduced >90% (p<0.01) in the Mac-1-/- mice. Neutrophil degranulation was investigated by measuring β-glucuronidase (a constituent of primary granules) in both peripheral and exudate neutrophils after 4 hours of thioglycollate induced peritonitis. Peritoneal exudate neutrophils in the Mac-1-/- mice retained more than 75% of their β-glucuronidase compared to peripheral neutrophils, while wild-type (+/+) litter mates retained 30% of the enzyme (p<0.05). These results support the conclusion that emigration of neutrophils into the peritoneal cavity does not require Mac-1-dependent adhesion, but the degranulation that is associated with neutrophil extravasation is heavily dependent on Mac-1 adhesion.