Neutrophil emigration in the skin, lungs, and peritoneum: different requirements for CD11/CD18 revealed by CD18-deficient mice.
To determine the role of CD11/CD18 complexes in neutrophil emigration, inflammation was induced in the skin, lungs, or peritoneum of mutant mice deficient in CD18 (CD18-/- mutants). Peripheral blood of CD18-/- mutants contained 11-fold more neutrophils than did blood of wild-type (WT) mice. During irritant dermatitis induced by topical application of croton oil, the number of emigrated neutrophils in histological sections of dermis was 98% less in CD18-/- mutants than in WT mice. During Streptococcus pneumoniae pneumonia, neutrophil emigration in CD18-/- mutants was not reduced. These data are consistent with expectations based on studies using blocking antibodies to inhibit CD11/CD18 complexes, and on observations of humans lacking CD11/CD18 complexes. The number of emigrated neutrophils in lung sections during Escherichia coli pneumonia, or in peritoneal lavage fluid after 4 h of S. pneumoniae peritonitis, was not reduced in CD18-/- mutants, but rather was greater than the WT values (240 +/- 30 and 220 +/- 30% WT, respectively). Also, there was no inhibition of neutrophil emigration during sterile peritonitis induced by intraperitoneal injection of thioglycollate (90 +/- 20% WT). These data contrast with expectations. Whereas CD11/CD18 complexes are essential to the dermal emigration of neutrophils during acute dermatitis, CD18-/- mutant mice demonstrate surprising alternative pathways for neutrophil emigration during pneumonia or peritonitis.
Mizgerd
J P
JP
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Kubo
H
H
Kutkoski
G J
GJ
Bhagwan
S D
SD
Scharffetter-Kochanek
K
K
Beaudet
A L
AL
Doerschuk
C M
CM
D000818:Animals; D018845:CD11 Antigens / Q000096:biosynthesis / Q000502:physiology*; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology*; D017453:Dermatitis, Irritant / Q000235:genetics / Q000276:immunology; D004487:Edema / Q000235:genetics / Q000276:immunology; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology*; D007964:Leukocytosis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D010537:Peritoneum / Q000276:immunology* / Q000473:pathology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology; D011654:Pulmonary Edema / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology
D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules