Circulating WBCs and Neutrophils during Streptococcal Pneumonia

The roles of selectins in the pulmonary margination and emigration of neutrophils were investigated by using mice genetically deficient in both Eand P-selectins (E/P mutants) and/or by intravenous injections of fucoidin (inhibiting both Land P-selectins). E/P mutants were neutrophilic (14.7 + 4.9 • 106 vs. 0.8 + 0.1 • 10 ~' neutrophils/ml). This neutrophilia was associated with increased margmation ofneutrophils 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 pneumonia< lungs o f E / P nmtants displayed increased neutrophil emigration (564 --+ 92 vs. 116 --19 neutrophils per 100 alveolar profiles), edema (5.3 + 1.5 vs. 1.5 • 0.4 ~l/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 W T or E/P mice. During pneumonia, the number of white blood ceils (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 Eand P-selectins; that streptococcal pneumonia induces an Eand 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.