Platelet-Dependent Generation of Chemotactic Activity in Serum

Abstract

The recognition that different host defense mechanisms against injury are closely interrelated has permitted a clearer understanding of the processes of inflammation, blood coagulation, and activation of serum proteolytic enzyme systems. Human blood platelets are cells primarily specialized for hemostasis. However, they have also been found to possess inflammatory functions characteristic of polymorphonuclear leukocytes and may therefore play a broader role in host defenses (1).Leukocytes promote inflammatory responses by releasing mediators of vascular permeability and mast cell degranulation, bactericidal proteins, chemotactic factors, and lysosomal enzymes that cause tissue damage (2). Platelets also release mediators of vascular permeability (3) and bactericidal proteins (4) and possess enzymes that damage elastic tissue and collagen (5, 6).This study has examined the role of platelets in the production of chemotactic activity for leukocytes and presents evidence that activation of the complement system b y platelets is a physiologic process that forms a link between the hemostatic process and inflammation. Materials and Methods Preparation of Platelets and PlateletFractions.--Human platelet concentrates were prepared from whole blood anticoagulated with acid citrate dextrose and kindly supplied by the New York Blood Center and the Memorial Hospital (New York) donor room. Platelets were separated and extensively washed by methods previously described in detail (3). Contamination by leukocytes was less than 1 per 104 platelets. The isolated platelets were briefly sonicared using a Branson Sonifier (Branson Instruments Co., Stanford, Conn.) and were extracted once with ice-cold 0.2 N H2SO4 for 1 h. Acid extracts were cleared by centrifugafion at 12,000 g and were dialyzed against buffered saline for 4 h at 10°C before experimental use. Dialyzed material was filtered through 0.45-/zm pore filters (Millipore Corp., Bedford, Mass.) and used immediately or stored at --20°C for up to 2 wk.Isolated platelet granules were obtained by sucrose density gradient centrifugation of

Human platelet-initiated formation and uptake of the C5-9 complex of human complement.

“…Weksler and Coupal (24) have demonstrated that a factor present in an acid-soluble extract of human platelets can release chemotactically active C5a from C5. At the present time it is not certain whether the property of human platelets that initiates formation of the C5-9 complex is related to the C5-splitting activity described by these investigators.…”

“…This reaction proceeds in the presence of EDTA and epsilonamino-N-caproic acid (EACA), suggesting that it is not initiated by the classical or alternative pathways of complement activation and also differs from C5-cleaving platelet factor of Weksler and Coupal (24). METHODS Preparation of platelet-rich plasma, washed platelets, washed erythrocytes, platelet-free plasma, and serum.…”

Human Platelet Collagenase

“…Since the platelet and granulocyte evolved from a common cell, the amebocyte (41), it was not surprising to find collagenase activity in the platelet granules. Indeed, an increasing number of proteins thought to be characteristic of leukocytes has been demonstrated in platelets, including mediators of vascular permeability (42), bacteriocidal process (43), elastic tissue destruction (3), and chemotaxis (44). This study indicates that collagenase, perhaps derived from the granules of platelets, may be available under certain conditions to play a role in the inflammatory process.…”

Effects of platelet release products on neutrophilic Fcγ receptors

“…Platelets have been shown to influence a wide variety of physiological processes of not only hemostasis but also inflammation through the actions of released products [1][2][3][4][5][6]. It has been reported that platelet release products (PRPr) involve several substances that enhance human leukocytic phagocytosis [7,8].…”