Tissue-Specific Mechanisms Control the Retention of IL-8 in Lungs and Skin

Abstract

Chemokines are a group of structurally related peptides that promote the directed migration of leukocytes in tissue. Mechanisms controlling the retention of chemokines in tissue are not well understood. In this study we present evidence that two different mechanisms control the persistence of the CXC chemokine, IL-8, in lungs and skin. 125I-labeled IL-8 was injected into the airspaces of the lungs and the dermis of the skin and the amount of 125I-labeled IL-8 that remained at specified times was measured by scintillation counting. The 125I-labeled IL-8 was cleared much more rapidly from skin than lungs, as only 2% of the 125I-labeled IL-8 remained in skin at 4 h whereas 50% of the 125I-labeled IL-8 remained in lungs at 4 h. Studies in neutropenic rabbits showed that neutrophils shortened the retention of 125I-labeled IL-8 in skin but not lungs. A monomeric form of IL-8, N-methyl-leucine 25 IL-8, was not retained as long in lungs as recombinant human IL-8, indicating that dimerization of IL-8 is a mechanism that increases the local concentration and prolongs the retention of 125I-labeled IL-8 in lungs. These observations show that the mechanisms that control the retention of IL-8 in tissue include neutrophil migration and dimerization, and that the importance of these varies in different tissues.