title: The differential roles of LFA-1 and Mac-1 in host defense against systemic infection with Streptococcus pneumoniae.
abstract: Mice deficient in CD18, which lack all four CD11 integrins, have leukocytosis and increased susceptibility to bacterial infection. To determine the effect of deficiencies in LFA-1 (CD11a/CD18) or Mac-1 (CD11b/CD18) on host defense against systemic bacterial infection, knockout mice were inoculated i.p. with Streptococcus pneumoniae. Increased mortality occurred in both LFA-1(-/-) (15 of 17 vs 13 of 35 in wild type (WT), p < 0.01) and Mac-1(-/-) (17 of 34 vs 6 of 25, p < 0.01) mice. All deaths in LFA-1(-/-) mice occurred after 72 h, whereas most deaths in Mac-1(-/-) mice occurred within 24-48 h. At 24 h, 21 of 27 Mac-1(-/-) mice were bacteremic, vs 15 of 25 WT (p = 0.05); no difference was observed between LFA-1(-/-) and WT. Increased bacteria were recovered from Mac-1(-/-) spleens at 2 h (p = 0.03) and 6 h (p = 0.002) and from livers (p = 0.001) by 6 h. No difference was observed at 2 h in LFA-1(-/-) mice, but by 6 h increased bacteria were recovered from spleens (p = 0.008) and livers (p = 0.04). Baseline and peak leukocyte counts were similar between Mac-1(-/-) and WT, but elevated in LFA-1(-/-). At 8 h, peritoneal neutrophils were increased in Mac-1(-/-), but not significantly different in LFA-1(-/-). Histopathologically, at 24 h Mac-1(-/-) animals had bacteremia and lymphoid depletion, consistent with sepsis. LFA-1(-/-) mice had increased incidence of otitis media and meningitis/encephalitis vs WT at 72 and 96 h. Both Mac-1 and LFA-1 play important but distinct roles in host defense to S. pneumoniae.
authors.affiliation: Section of Atherosclerosis, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Prince
authors.forename: C F
authors.initials: CF
authors.lastname: Brayton
authors.forename: M C
authors.initials: MC
authors.lastname: Fossett
authors.forename: J A
authors.initials: JA
authors.lastname: Durand
authors.forename: S L
authors.initials: SL
authors.lastname: Kaplan
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
authors.forename: C M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000097:blood; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000401:mortality; D006801:Humans; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D016920:Meningitis, Bacterial / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008586:Meningitis, Pneumococcal / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008590:Meningoencephalitis / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010033:Otitis Media / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification; D016019:Survival Analysis
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen