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 106 vs. 0.8 ± 0.1 x 106 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 cells 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 μl/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