Immunocytochemical Localization of the Chemokines RANTES and MIP-1α within Human Platelets and Their Release during Storage

Abstract

The cytokines RANTES and MlP-1α are 8-kD peptides which belong to the C-C subfamily of chemokines. They are both potent chemotactic factors for basophils and eosinophils. Apart from lymphocytes, the RANTES peptides was recently shown to be released from human platelets stimulated with thrombin [Kameyoshi et al: J Exp Med 1992;176:587–592]. Employing postembedding immunocytochemistry, we could detect RANTES and for the first time also MlP-1α within the α-granules of human platelets. To date, MlP-1α was not reported to occur in platelets. In slightly activated platelets, as found in stored platelet concentrates (PC), label for RANTES and MlP-1α could also be observed within cisterns of the open canalicular system and on the plasma membrane, indicating a release of both peptides. These findings were confirmed by in vitro studies in PC, by investigation of RANTES and MlP-1α release into the suspending medium. Over a period of 8 days, RANTES was steadily released in relatively high amounts, whereas MlP-1α was measured in rather small amounts in the suspending medium. As RANTES and MlP-1α, besides their chemotactic activity on eosinophils and basophils, are able to mediate the release of histamine, it is tempting to speculate about a participation of platelets in inflammatory reactions in which eosinophils and basophils are involved.

MIP-1alpha as a critical macrophage chemoattractant in murine wound repair.

“…3). In addition, the fibrin clot was noted to stain positively, perhaps reflecting platelet-derived MIP-1␣ (not shown) (31).…”

“…At least two sources of MIP-1␣ occur in wounds. First, MIP-1␣ is found in platelets, and some MIP-1␣ may be quickly released from platelets as wound hemostasis occurs (31). In addition, immunolocalization suggests that macrophages within the wound are also a source of MIP-1␣.…”

Higher macrophage inflammatory protein (MIP)-1α and MIP-1β levels from CD8+T cells are associated with asymptomatic HIV-1 infection

“…Moreover, our analysis demonstrated a lack of correlation between CD4 ϩ and CD8 ϩ T-cell counts and plasma levels of MIP-1␤ or RANTES, although a statistically significant correlation was observed with MIP-1␣. Given that chemokines aggregate, adhere to extracellular carbohydrates, and arise from platelets during sample collection (60,61), these results should not be surprising. Indeed, our analysis showed no correlation between plasma levels of ␤ chemokines and the ability of CD8 ϩ T cells to release these molecules.…”

Spontaneous and antigen-induced production of HIV-inhibitory β-chemokines are associated with AIDS-free status

“…Activated platelets produce high quantities of chemokines, especially RANTES (45)(46)(47)(48)(49). Other studies performed by analyzing plasma͞serum levels of ␤-chemokines that did not show a positive effect of chemokines in HIV infection (50)(51)(52)(53)(54)(55)(56) probably were affected by this unspecific release.…”