Background: The majority of circulating monocytes exist in a classical phenotype (CD14⁺, CD16^low). Intermediate phenotype monocytes (CD14⁺, CD16^high) are normally rare but greatly expand in a range of disease conditions including sepsis, coronary artery disease and autoimmune disease, where their presence is associated with poor outcome. Using in vitro culture models it has previously been suggested that platelets can induce changes in monocyte phenotype, however, whether these can occur in physiological conditions and timescales remain unknown.

Aims: To investigate whether acute stimulation of platelets can switch monocytes from classic to intermediate phenotype in whole blood ex vivo.

Methods: Whole blood was stimulated with collagen-related peptide (CRP-XL) and mixed at 37°C for 10-120 minutes. Flow cytometric analysis was performed to detect CD14⁺ monocytes, their subtype (classical CD16^low; intermediate CD16^High) and the presence or absence of platelets (CD42b). Further cell markers were incorporated to detect altered expression profiles. Data are mean ±s.e.m from n=7.

Results: CRP-XL stimulated platelets to bind to CD14⁺ monocytes within 10 minutes (66±4% vs 19±3% vehicle). Concurrently, within 10 minutes, there was a proportional decrease in classical monocytes from 80±1% to 38±9% (p< 0.05) and the intermediate subset increased from 4±1% to 42±6% (p< 0.05). This response was maintained and unchanged for up to 2 hours. Of this intermediate subset, post CRP-XL stimulation, 91±2% were platelet positive. Furthermore a significant increase (52±11%) in pro-chemotactic CCR2 expression and a significant decrease (28±7%) in antigen-presenting HLA-DR expression was observed only in platelet-induced intermediate monocyte subset and not platelet-bound classical monocytes.

Conclusions: Direct and selective activation of platelets in whole blood results in rapid emergence of a platelet-induced intermediate subset of monocytes with differential receptor expression.
These data strongly indicate a role for platelets as rapid regulators of monocyte phenotype and identify a potential means to control disease-associated monocyte phenotypes.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelets-induce-rapid-subset-and-phenotypic-switching-in-monocytes-in-whole-blood/