title: P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli.
abstract: Neutrophil emigration during an inflammatory response is mediated through interactions between adhesion molecules on endothelial cells and neutrophils. P-Selectin mediates rolling or slowing of neutrophils, while intercellular adhesion molecule-1 (ICAM-1) contributes to the firm adhesion and emigration of neutrophils. Removing the function of either molecule partially prevents neutrophil emigration. To analyze further the role of P-selectin and ICAM-1, we have generated a line of mice with mutations in both of these molecules. While mice with either mutation alone show a 60-70% reduction in acute neutrophil emigration into the peritoneum during Streptococcus pneumoniae-induced peritonitis, double mutant mice show a complete loss of neutrophil emigration. In contrast, neutrophil emigration into the alveolar spaces during acute S. pneumoniae-induced pneumonia is normal in double mutant mice. These data demonstrate organ-specific differences, since emigration into the peritoneum requires both adhesion molecules while emigration into the lung requires neither. In the peritoneum, P-selectin-independent and ICAM-1-independent adhesive mechanisms permit reduced emigration when one of these molecules is deficient, but P-selectin-independent mechanisms cannot lead to ICAM-1-independent firm adhesion and emigration.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Bullard
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: I
authors.initials: I
authors.lastname: Lorenzo
authors.forename: W M
authors.initials: WM
authors.lastname: Quinlin
authors.forename: N A
authors.initials: NA
authors.lastname: Doyle
authors.forename: R
authors.initials: R
authors.lastname: Bosse
authors.forename: D
authors.initials: D
authors.lastname: Vestweber
authors.forename: C M
authors.initials: CM
authors.lastname: Doerschuk
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004487:Edema / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007958:Leukocyte Count; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin; D010529:Peritoneal Cavity / Q000166:cytology / Q000502:physiology*; D010538:Peritonitis / Q000503:physiopathology; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D011008:Pneumococcal Infections / Q000503:physiopathology; D018410:Pneumonia, Bacterial / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1