Phagocytic Integrins: Activation and Signaling

Torres-Gómez, Álvaro; Cabañas, Carlos; Lafuente, Esther M.

doi:10.3389/fimmu.2020.00738

Cited by 59 publications

(54 citation statements)

References 163 publications

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“…Cold‐induced damaged PLT lesions include reorganization of membrane GPs (eg, GPIa, GPIIb/IIIa, 9–11 which result in recognition and clearance by internalization (phagocytosis) mediated by macrophage integrins (α M β 2 integrin, 35 or hepatocyte Ashwell‐Morell receptors 36 9 .…”

Section: Resultsmentioning

confidence: 99%

Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage

et al. 2020

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Background Cold storage of platelets (PLTs) has the potential advantage of prolonging storage time while reducing posttransfusion infection given the decreased likelihood of bacterial outgrowth during storage and possibly beneficial effects in treating bleeding patients. However, cold storage reduces PLT survival through the induction of complex storage lesions, which are more accentuated when storage is prolonged. Study Design and Methods Whole blood–derived PLT‐rich plasma concentrates from seven PLT pools (n = 5 donors per pool). PLT additive solution was added (67%/33% plasma) and the product was split into 50‐mL bags. Split units were stored in the presence or absence of 1 mM of N‐acetylcysteine (NAC) under agitation for up to 14 days at room temperature or in the cold and were analyzed for PLT activation, fibrinogen‐dependent spreading, microparticle formation, mitochondrial respiratory activity, reactive oxygen species (ROS) generation, as well as in vivo survival and bleeding time correction in immunodeficient mice. Results Cold storage of PLTs for 7 days or longer induces significant PLT activation, cytoskeletal damage, impaired fibrinogen spreading, enhances mitochondrial metabolic decoupling and ROS generation, and increases macrophage‐dependent phagocytosis and macrophage‐independent clearance. Addition of NAC prevents PLT clearance and allows a correction of the prolonged bleeding time in thrombocytopenic, aspirin‐treated, immunodeficient mice. Conclusions Long‐term cold storage induces mitochondrial uncoupling and increased proton leak and ROS generation. The resulting ROS is a crucial contributor to the increased macrophage‐dependent and ‐independent clearance of functional PLTs and can be prevented by the antioxidant NAC in a magnesium‐containing additive solution.

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Section: Resultsmentioning

confidence: 99%

Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage

et al. 2020

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“…The importance of CR3 is highlighted by its contribution to both the recruitment of leukocytes (via adhesion) and phagocytosis of targets. CR4, which contains the CD11c α-chain instead, is highly expressed in monocytes, macrophages and DCs, where it mediates similar functions to CR3 (Torres-Gomez et al, 2020a ). For a detailed description of CR3 and CR4 structure and motifs, see section β2-Integrin Family Complement Receptors CR3 and CR4.…”

Section: Role Of Complement Receptors In Phagocytosismentioning

confidence: 99%

Complement Receptors and Their Role in Leukocyte Recruitment and Phagocytosis

Vandendriessche

Cambier

Proost

et al. 2021

Front. Cell Dev. Biol.

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The complement system is deeply embedded in our physiology and immunity. Complement activation generates a multitude of molecules that converge simultaneously on the opsonization of a target for phagocytosis and activation of the immune system via soluble anaphylatoxins. This response is used to control microorganisms and to remove dead cells, but also plays a major role in stimulating the adaptive immune response and the regeneration of injured tissues. Many of these effects inherently depend on complement receptors expressed on leukocytes and parenchymal cells, which, by recognizing complement-derived molecules, promote leukocyte recruitment, phagocytosis of microorganisms and clearance of immune complexes. Here, the plethora of information on the role of complement receptors will be reviewed, including an analysis of how this functionally and structurally diverse group of molecules acts jointly to exert the full extent of complement regulation of homeostasis.

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“…Such an effect is critical in the case of MerTK which itself does not bind F-actin directly or even, to our knowledge, indirectly. Since integrins provide the mechanical linkage between actin polymerization to the ruffling/ensheathing membrane to yield traction, it makes sense that their activation by primary phagocytic receptors is observed in many types of phagocytosis (84). In this regard, it is noteworthy that MerTK-mediated phagocytosis involves focal adhesion kinase (FAK) (85), regulation of FAK activity (62), and the cleavage of PtdIns(4,5) P 2 to generate Ins3P/diacylglycerol (DAG), which are normally associated with integrin and Rap activation respectively (86).…”

Section: Crosstalk Between Mertk and Avb5mentioning

confidence: 99%