Targeted disruption of the β-chemokine receptor CCR1 protects against pancreatitis-associated lung injury

β-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 β-chemokine receptors has been identified, four of which are capable of recognizing the chemokines MIP1α and RANTES. Genetic deletion of one of the MIP1α and RANTES receptors, CCR5, is associated with protection from infection with HIV-1 in humans, while deletion of the ligand MIP1α protects against Coxsackie virus-associated myocarditis. In this report we show that the deletion of another receptor for MIP1α 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-α in a temporal sequence indicating that the activation of the CCR1 receptor is an early event in the systemic inflammatory response syndrome.