Recent Advances in the Discovery and Function of Antimicrobial Molecules in Platelets

Abstract

The conventional function described for platelets is maintaining vascular integrity. Nevertheless, increasing evidence reveals that platelets can additionally play a crucial role in responding against microorganisms. Activated platelets release molecules with antimicrobial activity. This ability was first demonstrated in rabbit serum after coagulation and later in rabbit platelets stimulated with thrombin. Currently, multiple discoveries have allowed the identification and characterization of PMPs (platelet microbicidal proteins) and opened the way to identify kinocidins and CHDPs (cationic host defense peptides) in human platelets. These molecules are endowed with microbicidal activity through different mechanisms that broaden the platelet participation in normal and pathologic conditions. Therefore, this review aims to integrate the currently described platelet molecules with antimicrobial properties by summarizing the pathways towards their identification, characterization, and functional evaluation that have promoted new avenues for studying platelets based on kinocidins and CHDPs secretion.

Human Platelets Contain, Translate, and Secrete Azurocidin; A Novel Effect on Hemostasis

“…Platelets are the smallest circulating cells primarily involved in hemostasis but have gained interest due to their participation in divergent functions, including the immune response. In innate host defense, platelets produce antimicrobial and chemoattractant mediators [ 6 , 21 ]. Nevertheless, the presence of azurocidin protein in platelets and megakaryoblasts had not been fully characterized.…”

“…We subsequently confirmed the expression of azurocidin protein, within the α-granule, of both platelets and Meg-01 cells, in the latter also in an extra-granular manner. In addition to azurocidin, it is now known that α-granules contain a variety of molecules with microbicidal activity, such as Basic Platelet Protein (PBP), CXCL4, CCL5, and HNP-1 (defensin-α1) [ 6 ]. Recently, it has been shown that megakaryocytes contain and transfer defensin-α1 to nascent platelets, although they can also acquire it from plasma [ 23 ].…”

“…As part of their participation in the innate immune response, platelets contain molecules with antimicrobial activity, such as kinocidins; CXCL4, CXCL7, and CCL5, and cationic host defense peptides (CHDPs); human neutrophil peptide (HNP) 1, human beta-defensins (HBD) 1–3, and cathelicidin LL-37. Different stimuli such as lipopolysaccharide (LPS), Adenosine diphosphate (ADP), and mainly thrombin induce the secretion of microbicidal molecules from platelets [ 6 ]. A clear example of a platelet molecule with microbicidal action is CXCL4 (PF4, platelet factor 4), a very abundant protein in platelet granule-α and one of its main secretion products; CXCL4 has a broad spectrum of antimicrobial action, including on bacteria as E. coli , S. aureus , and S. typhimurium ; fungus as C. albicans , as well as the antiviral response against human immunodeficiency virus (HIV) and influenza A virus (IAV) [ 6 , 7 ].…”

“…Different stimuli such as lipopolysaccharide (LPS), Adenosine diphosphate (ADP), and mainly thrombin induce the secretion of microbicidal molecules from platelets [ 6 ]. A clear example of a platelet molecule with microbicidal action is CXCL4 (PF4, platelet factor 4), a very abundant protein in platelet granule-α and one of its main secretion products; CXCL4 has a broad spectrum of antimicrobial action, including on bacteria as E. coli , S. aureus , and S. typhimurium ; fungus as C. albicans , as well as the antiviral response against human immunodeficiency virus (HIV) and influenza A virus (IAV) [ 6 , 7 ]. In addition to the above, it has been described that those molecules with antimicrobial activity can induce [ 8 , 9 ] or inhibit [ 10 ] platelet aggregation, increasing the evidence of the functional link between hemostasis and platelet immune response.…”

Tumour cell-activated platelets modulate the immunological activity of CD4+, CD8+, and NK cells, which is efficiently antagonized by heparin

“…Besides their crucial role in haemostasis, platelets are progressively considered as immune-competent cells participating in inflammation and immunity. Platelets were shown to directly contribute to anti-viral and anti-bacterial immunity by release of microbicidal factors, pathogen engulfment or aggregate formation [9][10][11]. In particular, by interaction with lymphocytes platelets are capable of affecting their immunological functions.…”