title: Inhibition of alveolar neutrophil immigration in endotoxemia is macrophage inflammatory protein 2 independent.
abstract: BACKGROUND
  Altered transendothelial migration and delayed apoptosis of neutrophils (PMN) have been implicated as contributing to infection in patients with gram-negative sepsis. Macrophage inflammatory protein 2 (MIP-2) signals PMN immigration and may alter other PMN functions. We tested the hypothesis that sequential endotoxin challenge in vivo alters PMN apoptosis and chemotactic responses.
  
  
  METHODS
  Endotoxemia was induced in male Wistar rats (250 g) via intraperitoneal (IP) administration of LPS (4 mg/kg). After 18 h, intratracheal (IT) injection of LPS (400 microg/kg) was performed. Control animals received saline injections. Four hours after IT-LPS, circulating and bronchoalveolar lavage (BAL) PMN were isolated. PMN yields were calculated, and apoptosis was quantified after 18 h in culture by annexin V-fluorescein isothiocyanate FACS analysis. BAL MIP-2 concentrations were determined by ELISA. PMN chemotaxis to MIP-2 and IL-8 was determined using a fluorescent in vitro migration assay.
  
  
  RESULTS
  Endotoxemia (IP-LPS) significantly decreases BAL PMN yield in response to an in vivo IT-LPS challenge. IT-LPS inhibits BAL PMN apoptosis to the same extent as sequential IP/IT-LPS. Alveolar MIP-2 concentrations are similar in the two groups. In vitro migration to IL-8 and MIP-2 was inhibited in PMN from endotoxemic versus control animals.
  
  
  CONCLUSIONS
  These data demonstrate that endotoxemia inhibits PMN migration despite similar MIP-2 concentrations in the alveolus. Sequential insults do not affect the inhibition of apoptosis. In vitro, PMN from endotoxemic animals display impaired chemotaxis to MIP-2 and interleukin-8. This may result in an inadequate host defense that contributes to increased ICU-acquired pneumonia in septic patients.
authors.affiliation: Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Duffy
authors.forename: B
authors.initials: B
authors.lastname: Nolan
authors.forename: K
authors.initials: K
authors.lastname: Sheth
authors.forename: H
authors.initials: H
authors.lastname: Collette
authors.forename: M
authors.initials: M
authors.lastname: De
authors.forename: P E
authors.initials: PE
authors.lastname: Bankey
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement; D054426:Chemokine CXCL2; D019446:Endotoxemia / Q000276:immunology*; D016209:Interleukin-8 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D015846:Monokines / Q000032:analysis / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D019707:Receptors, Chemokine / Q000502:physiology; D018123:Receptors, Interleukin / Q000502:physiology; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B
chemical_list: D015703:Antigens, CD; D054426:Chemokine CXCL2; D016209:Interleukin-8; D008070:Lipopolysaccharides; D015846:Monokines; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B