Selectins and neutrophil traffic: margination and Streptococcus pneumoniae-induced emigration in murine lungs.
The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both E- and P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both L- and P-selectins). E/P mutants were neutrophilic (14.7 +/- 4.9 x 10(6) vs. 0.8 +/- 0.1 x 10(6) neutrophils/ml). This neutrophilia was associated with increased margination of neutrophils within pulmonary capillaries (39.7 +/- 9.4 vs. 4.6 +/- 1.1 neutrophil profiles per 100 red blood cell profiles) but no change in margination within noncapillary pulmonary microvessels. After intratracheal instillation of Streptococcus pneumoniae, lungs of E/P mutants displayed increased neutrophil emigration (564 +/- 92 vs. 116 +/- 19 neutrophils per 100 alveolar profiles), edema (5.3 +/- 1.5 vs. 1.5 +/- 0.4 microliter/g body weight), and histologic evidence of lung injury compared with those in wild-type (WT). Fucoidin treatment did not affect neutrophil emigration during streptococcal pneumonia in WT or E/P mice. During pneumonia, the number of white blood cells (WBC) tethered to or spread upon the noncapillary vessel endothelium increased in both WT and E/P lungs. These are the first data demonstrating that neutrophil margination in uninfected pulmonary capillaries does not require E- and P-selectins; that streptococcal pneumonia induces an E- and P-selectin-independent increase in WBC interactions with noncapillary endothelium; and that migration of neutrophils to alveoli can occur despite deficiency or inhibition of all of the known selectins.
Mizgerd
J P
JP
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Meek
B B
BB
Kutkoski
G J
GJ
Bullard
D C
DC
Beaudet
A L
AL
Doerschuk
C M
CM
D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D011654:Pulmonary Edema / Q000473:pathology; D019087:Selectins / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*
D019087:Selectins