L-SELECTIN (CD62L) BLOCKADE DOES NOT IMPAIR PERITONEAL NEUTROPHIL EMIGRATION OR SUBCUTANEOUS HOST-DEFENSE TO BACTERIA IN RABBITS

Neutrophil (PMN) recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence, We explored the role of L-selectin (CD62L) in leukocyte emigration fo llowing instillation of bacteria into the peritoneum or s.c. skin in r abbits, Pretreatment with blocking mAb against L-selectin (LAM1,3) red uced peritoneal PMN emigration 4 h after i.p. inoculation with 10(10) CFU of Escherichia coli by only 17% compared with animals receiving a nonblocking L-selectin mAb (LAM1.14). Peritoneal PMNs from saline-trea ted rabbits demonstrated a complete absence of L-selectin, whereas tho se from LAM1.3-treated animals retained 43% of their baseline L-select in expression. This suggests that L-selectin shedding is not a requisi te event for PMN emigration under these conditions, In rabbits given s .c. inoculations with either Staphylococcos aureos or E. coli, pretrea tment with mAb LAM1.3 did not significantly impair PMN emigration at 2 4 h, nor increase the incidence, size, or associated mortality of resu lting abscesses at 7 days compared with animals receiving nonblocking mAb LAM1.14. We conclude that: 1) mAb blockade of L-selectin in vivo o nly modestly affects acute, E. coli-induced peritoneal PMN emigration; and 2) L-selectin blockade does not increase infectious sequelae asso ciated with s.c. bacterial inoculation, These findings of only mildly reduced PMN emigration into the peritoneum and no alteration in s.c. h ost defense differ from those reported with L-selectin blockade under other, nonbacterial inflammatory conditions, and suggest that redundan t selectin-mediated mechanisms (P- and E-selectin) are sufficient for normal PMN emigration in response to bacterial stimulation.