Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury.
beta-Chemokines and their receptors mediate the trafficking and activation of a variety of leukocytes including the lymphocyte and macrophage. An array of no less than eight beta-chemokine receptors has been identified, four of which are capable of recognizing the chemokines MIP1alpha and RANTES. Genetic deletion of one of the MIP1alpha and RANTES receptors, CCR5, is associated with protection from infection with HIV-1 in humans, while deletion of the ligand MIP1alpha protects against Coxsackie virus-associated myocarditis. In this report we show that the deletion of another receptor for MIP1alpha and RANTES, the CCR1 receptor, is associated with protection from pulmonary inflammation secondary to acute pancreatitis in the mouse. The protection from lung injury is associated with decreased levels of TNF-alpha in a temporal sequence indicating that the activation of the CCR1 receptor is an early event in the systemic inflammatory response syndrome.
Gerard
C
C
Ina Sue Perlmutter Laboratory, Children's Hospital, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School and the Center for Blood Research, Boston, Massachusetts 02115, USA.
Frossard
J L
JL
Bhatia
M
M
Saluja
A
A
Gerard
N P
NP
Lu
B
B
Steer
M
M
D000818:Animals; D002199:Capillary Permeability; D002108:Ceruletide / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D017353:Gene Deletion; D008168:Lung / Q000737:chemistry; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008833:Microcirculation; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications*; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000235:genetics*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014867:Water / Q000032:analysis
C515301:Ccr1 protein, mouse; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D014867:Water; D002108:Ceruletide