Are Platelets Cells? And if Yes, are They Immune Cells?

Abstract

Small fragments circulating in the blood were formally identified by the end of the nineteenth century, and it was suggested that they assisted coagulation via interactions with vessel endothelia. Wright, at the beginning of the twentieth century, identified their bone-marrow origin. For long, platelets have been considered sticky assistants of hemostasis and pollutants of blood or tissue samples; they were just cell fragments. As such, however, they were acknowledged as immunizing (to specific HPA and HLA markers): the platelet’s dark face. The enlightened face showed that besides hemostasis, platelets contained factors involved in healing. As early as 1930s, platelets entered the arsenal of medicines were transfused, and were soon manipulated to become a kind of glue to repair damaged tissues. Some gladly categorized platelets as cells but they were certainly not fully licensed as such for cell physiologists. Actually, platelets possess almost every characteristic of cells, apart from being capable of organizing their genes: they have neither a nucleus nor genes. This view prevailed until it became evident that platelets play a role in homeostasis and interact with cells other than with vascular endothelial cells; then began the era of physiological and also pathological inflammation. Platelets have now entered the field of immunity as inflammatory cells. Does assistance to immune cells itself suffice to license a cell as an “immune cell”? Platelets prove capable of sensing different types of signals and organizing an appropriate response. Many cells can do that. However, platelets can use a complete signalosome (apart from the last transcription step, though it is likely that this step can be circumvented by retrotranscribing RNA messages). The question has also arisen as to whether platelets can present antigen via their abundantly expressed MHC class I molecules. In combination, these properties argue in favor of allowing platelets the title of immune cells.

Specific activation, signalling and secretion profiles of human platelets following PAR-1 and PAR-4 stimulation

“…Here, we investigated whether the platelet PAR-1 and PAR-4 play a major role concerning the modulation of platelet function as innate immunity receptors. Indeed, distinct signals engage differential activation and signalling pathways to induce secretion of haemostatic and BRM factor profiles [14][15][16]; our own conclusions differ from Van Holten et al [6], as we propose that platelets sense differentially PAR stimuli as they sense differentially microbial and other danger signals, adjusting response to stimulus variation [14,[17][18][19].…”

Transfusion as an Inflammation Hit: Knowns and Unknowns

“…Indeed, many studies have shown that platelets express a large variety of pathogen sensors, promptly engaged by several kinds of the so-called pathogen-associated molecular pattern (molecules) or PAMPs (if stresses are infectious in nature) or damage-associated molecular pattern (molecules) or DAMPs (if stresses are internal, such as Abs). This has been principally found relative to platelets (32, 33), and similar findings have been reported for erythrocytes (34). Furthermore, donor platelets express HLA class I Ags that differ in general from those of recipients.…”

“…Depending on the nature of this stress, platelets can mobilize predefined patterns of BRMs (88, 89). Indeed, contrary to what we might expect, given that they are anucleate, platelets do not indiscriminately release granule content through an all-or-nothing mechanism but rather exhibit stress-dictated processes (32, 90–93). This may explain why certain patients having received PCs manifest allergic reactions (where δ-granule BRMs predominate) or FNHTR/inflammation (where α-granule BRMs predominate) (Figure 1; Table 2).…”

Platelets Mediate Host Defense against Staphylococcus aureus through Direct Bactericidal Activity and by Enhancing Macrophage Activities

“…These mediators attract and modulate effector cells of the immune system. In addition, platelets themselves demonstrate direct effector function and should be regarded as effector immune cells (3). …”