Antibodies Directed to the Chemotactic Factor Receptor Detect Differences Between Chemotactically Normal and Defective Neutrophils From LJP Patients

Abstract

Localized juvenile periodontitis (ljp) is a progressively destructive infection of the supporting tissues of the teeth, primarily affecting adolescents. In this disease, patients' polymorphonuclear leukocytes (PMN) exhibit decreased Chemotaxis (CTX) and decreased binding of the chemotactic peptide N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenyl‐alanine (FMLP) to specific receptors on the PMN surface. Since the FMLP receptor is involved in the activation of the PMN, and its subsequent response to chemotactic stimuli, a decrease in the chemotactic peptide receptor, as seen in LJP patients, is suspected to be a predisposing factor for this disease. To define differences in the FMLP receptor between CTX defective LJP patients and CTX normal donors, a battery of monoclonal antibodies reactive against the FMLP receptor was prepared. The FMLP receptor was affinity‐purified, and was found to be comprised of two components, one of 68 kDa, and the other of 94 kDa. Only the 68 kDa component specifically bound a radioiodinated FMLP analogue in a photoaffinity experiment. Seven monoclonal antibodies were selected on the basis of their reactivity with the 68 kDa receptor component, and of these, 5 showed reduced binding against PMN from CTX defective LJP donors when compared to their reactivity against PMN from CTX normal subjects. Two of the 7 anti‐68 kDa antibodies reacted with PMN from both sets of subjects at a comparable extent. Furthermore, the presence of 20 nmol of FMLP inhibited the binding of 5 of the anti‐receptor antibodies to whole PMN, including one that showed no difference in binding between CTX normal and defective PMN, and 4 of the 5 that did show such difference. These results show that a difference in the binding of antibodies to the FMLP receptor complex exists between neutrophils from chemotactically depressed LJP patients as compared to normal controls. These differences in binding may be due to qualitative differences in the receptor or may represent reduced expression of receptor components on the surface of LJP neutrophils. These results add further support to the concept that alterations in the surface of PMN from LJP patients are associated with reduced Chemotaxis. J Periodontol 1990;61:609‐617.

Nupharidine enhances Aggregatibacter actinomycetemcomitans clearance by priming neutrophils and augmenting their effector functions

“…The response of diseased patients` primary neutrophils versus periodontally healthy neutrophils without Nupharidine reflects the well‐established neutrophils hypo‐function associated with aggressive periodontitis (DeNardin et al., ; Scott & Krauss, ; Shapira et al., ; Sigusch et al., ; Suzuki et al., ). The beneficial effect of Nupharidine on the diseased patients’ primary neutrophils may suggest that the Nupharidine priming of diseased patients` neutrophils recover neutrophils function to the functional levels of healthy neutrophils infected with Aa‐JP2.…”

“…Neutrophils play a crucial role in the clearance of pathogens, by various effector functions such as phagocytosis, degranulation and formation of neutrophil extracellular traps (NETs) (Scott & Krauss, 2012). Periodontitis in adolescents and young adults (formerly Aggressive Periodontitis) is associated with specific infection by Aggregatibacter actinomycetemcomitans, JP2 clone (Aa-JP2) (Haubek et al, 2008) and also with abnormal neutrophil function (DeNardin, DeLuca, Levine, & Genco, 1990;Scott & Krauss, 2012;Shapira, Borinski, Sela, & Soskolne, 1991;Sigusch, Eick, Pfister, Klinger, & Glockmann, 2001;Suzuki, Collison, Falkler, & Nauman, 1984). Classical studies have demonstrated that in this variant of periodontitis, neutrophils have impaired chemotaxis (DeNardin et al, 1990;Sigusch et al, 2001), defective phagocytosis (Suzuki et al, 1984) and increased superoxide production (Shapira et al, 1991).…”

“…Citrullination of proteins is a part of NET formation and therefore link NETosis to RA (Spengler et al, 2015); NETs are also currently studied in correlation to tumour formation, sepsis and their amplification in diabetic patients (Yang et al, 2016). On the other hand, it may increase neutrophil anti- The response of diseased patients` primary neutrophils versus periodontally healthy neutrophils without Nupharidine reflects the well-established neutrophils hypo-function associated with aggressive periodontitis (DeNardin et al, 1990;Scott & Krauss, 2012;Shapira et al, 1991;Sigusch et al, 2001;Suzuki et al, 1984). The beneficial effect of Nupharidine on the diseased patients' primary neutrophils may suggest that the Nupharidine priming of diseased patients` neutrophils recover neutrophils function to the functional levels of healthy neutrophils infected with Aa-JP2.…”

El neutrófilo y su importancia en la enfermedad periodontal

“…Existen diferentes causas, entre las que encontramos: disminución de IL-8 (11); disminución de C5a (11,12); disminución de fMLP (péptidos de N-formilmetionil) (12,13,14); y disminución de la glicoproteina superficial GP110 (15), aunque todavía existen dudas sobre su influencia.…”

Salivary Biochemistry in Buffalo: The Legacy of Michael J. Levine

“…So, for example, Tom van Dyke, and later Ernie DeNardin and Drew Dentino, pursued biochemical studies of neutrophil chemotaxis as related to localized juvenile periodontitis (Van Dyke et al, 1983;DeNardin et al, 1990;Dentino et al, 1991). For their PhD theses, Joe Zambon purified and characterized the polysaccharide capsule from Actinobacillus actinomycetem-comitans (Zambon et al, 1984), and Bob Schifferle the capsule from Porphyromonas gingivalis (Schifferle et al, 1989(Schifferle et al, , 1993a.…”