Platelet Microbicidal Activity Is an Important Defense Factor against Viridans Streptococcal Endocarditis

Abstract

To study the role of platelet microbicidal activity in host defense against infective endocarditis (IE) due to viridans streptococci (VS), the susceptibility to platelet releasate of blood and oral VS isolates from patients with and without IE was compared. The influence of neutralization of platelet microbicidal activity was studied in 2 experimental IE models. Resistance to platelet releasate was more prevalent among VS from blood of patients with IE than from blood of bacteremic patients without IE and among oral VS isolates. Serum from rabbits vaccinated with human platelet sonicate supernatants neutralized human and rabbit platelet-released microbicidal activity and had antibodies recognizing microbicidal proteins thrombocidin-1 and -2 and other human platelet proteins. In the 2 rabbit IE models, vaccination increased the susceptibility to experimental IE due to platelet releasate-susceptible VS. Thus, platelet-released microbicidal activity is an important host defense factor against IE due to VS.

Interleukin 1α Increases the Susceptibility of Rabbits to Experimental Viridans Streptococcal Endocarditis

“…inoculum of bacteria (13) colonizing the vegetations. The presence of the catheter enhanced the production and the further development of IE due to various bacterial species (7,8,17,19,40) and delayed spontaneous sterilization of infected vegetations (19,40).The infection-enhancing effect of the catheter has been explained by impairment of the host phagocytic defense (19,21). However, in monocytopenic (37) and granulocytopenic (28) rabbits, susceptibility to IE due to VS was not different from controls.…”

“…Another major determinant for the development of IE is the susceptibility of the circulating microorganisms to platelet microbicidal activity (2,(7)(8)(9) due to cationic proteins such as thrombocidin or platelet microbicidal proteins, released after thrombin stimulation (7,9,26,36,39). Neutralization of this defense mechanism enhanced susceptibility of rabbits to IE due to platelet releasate-susceptible VS (8).…”

“…Neutralization of this defense mechanism enhanced susceptibility of rabbits to IE due to platelet releasate-susceptible VS (8). Platelet microbicidal activity is very likely to operate in humans as well, as VS and Staphylococcus aureus isolated from vegetations of endocarditis patients are generally less susceptible than oral isolates (7,8,38).…”

“…Neutralization of this defense mechanism enhanced susceptibility of rabbits to IE due to platelet releasate-susceptible VS (8). Platelet microbicidal activity is very likely to operate in humans as well, as VS and Staphylococcus aureus isolated from vegetations of endocarditis patients are generally less susceptible than oral isolates (7,8,38). Despite an apparent selective advantage, the VS isolates from IE patients are presumably still subject to the platelet defense system, since these isolates are only slightly less susceptible to purified thrombocidins in vitro (9,41).…”

In Vitro Susceptibility to Thrombin-Induced Platelet Microbicidal Protein Is Associated With Reduced Disease Progression and Complication Rates in Experimental Staphylococcus aureus Endocarditis

“…6,7 A growing body of evidence strongly suggests that tPMPs serve an integral role in host defense by limiting the progression of endovascular infections. [11][12][13][14][15] However, the overall relationship between microbial tPMP-susceptibility phenotypes and complications in IE has not yet been addressed. In the present study, we evaluated whether microbial differences in tPMP-susceptibility phenotypes in vitro would affect key parameters related to IE severity and prognosis, including the frequency and extent of valvular and perivalvular complications.…”