Vascular surveillance by haptotactic blood platelets in inflammation and infection

Abstract

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.

The Relationship between the Mean Platelet Volume and Carotid Atherosclerosis and Prognosis in Patients with Acute Cerebral Infarction

“…An increase in MPV indicates that the body is in a potentially proinflammatory state and further cascades. The amplified inflammatory response can lead to aggravated destruction of the blood-brain barrier, causing secondary brain damage [ 20 , 21 ]. (2) The higher the risk of thrombosis in patients with high MPV levels, the greater the risk of thrombosis, which can cause repeated embolization of small blood vessels in the local brain tissue and aggravate nerves and functional impairment [ 22 ].…”

Interplay between inflammation and thrombosis in cardiovascular pathology

“…These cell types have a tightly regulated interplay, which has been uncovered during the past decade. Platelets can migrate within the vasculature — a process distinct from adhesion, aggregation or clot contraction — and function as mechano-scavengers that collect bacteria on their surface and present them to neutrophils 18 , 19 . Platelet migration is actomyosin dependent and mediated through the interaction of αIIbβ3 integrin with the surrounding fibrinogen environment.…”

Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia

“…This concept has been extended by Haile et al [53], arguing that PF4 plays a broad role in innate immunity and inflammatory responses. Besides these PF4-related interactions, PF4-independent platelet-bacterial interactions are an accepted general mechanism of host defense [54,55].…”