Neutrophils enhance the clearance of systemic amyloid deposits in a murine amyloidoma model.

Introduction: Amyloid-specific antibodies have been shown to opsonize and enhance amyloid clearance in systemic amyloidosis mouse models. However, the immunological mechanisms by which amyloid is removed have not been clearly defined. Previous reports from preclinical Methods: Immunocompromised nude mice injected subcutaneously with patient-derived AL amyloid extract (generating a localized "amyloidoma") were used to circumvent confounding factors contributed by the adaptive immune system and served as the model system. Two representative AL amyloid extracts were used, ALλ(CLA), which is refractory to clearance, and ALκ(TAL), which is readily cleared in mice. Neutrophil recruitment to the amyloid masses, cellular activation, and propensity to engulf amyloid were assessed. Results: Immunophenotyping of amyloidomas from animals implanted with 2 mg of either ALλ or ALκ revealed that more neutrophils were recruited to ALκ amyloid masses as compared to the ALλ material, which was generally devoid of neutrophils. Discussion: Neutrophils may not directly mediate amyloid clearance through phagocytosis; however, these cells can be stimulated by the amyloid and may function to facilitate phagocytosis and amyloid clearance by professional phagocytes (