The tumor necrosis factor (TNF) locus contains the three closely related cytokine genes: TNF, and lymphotoxin α and �. The gene cluster lies at the telomeric end of the class III region of the major histocompatibility complex (MHC) approximately 1 megabase telomeric to the human leukocyte anti ...
The human genome contains 50,000–100,000 microsatellite repeats of (CA)n occurring every 30–60 kb in euchromatic regions of DNA (1). Their characteristic length polymorphism is probably due to DNA slippage during replication (2). While the normal function of microsatellite loci rem ...
Adhesion molecules mediate recognition of the blood vessels by circulating leukocytes and support their selective targeting to different organs (1). In the vessels, the blood flow imposes peculiar conditions by generating a wall shear stress that opposes leukocyte stable arrest on t ...
On circulating leukocytes, including monocytes and lymphocytes, α4-integrins are expressed in a low-affinity conformation. Low-affinity interactions with its ligand, vascular cell adhesion molecule-1 (VCAM-1), result in leukocyte tethering and rolling under flow (1,2), whe ...
Chemokines are a family of structurally related, small chemoattractant proteins that interact with specific seven-transmembrane, G-protein-coupled receptors that mediate cell migration in chemotactic gradients (1,2). Chemokine-receptor expression is finely regul ...
Leukocyte recruitment has been recognized as an early event in inflammatory processes since the late 19th century. Accumulation and trafficking of leukocytes in tissues under physiological and pathological conditions are orderly (typically neutrophils precede mononucl ...
Leukocyte recruitment to inflamed and lymphoid tissues is mediated by sequential adhesive interactions between specialized vascular receptors and their endothelial counterligands (1–3). Following rolling and arrest on the endothelium, circulating immune cells locomo ...
Angiogenesis is defined as the generation of new blood vessels from preexisting ones. Physiologic angiogenesis is a controlled and fundamental process during embryonic development, being rare in the adult and limited to conditions such as wound healing and menstrual cycle. If regula ...
Leukocyte migration into the brain represents a critical step in the inflammatory pathologies of the central nervous system (CNS). Leukocytes extravasate through the blood-brain barrier (BBB) during cerebrovascular diseases, infections, autoimmune diseases, traumas, tum ...
Viruses modulate the chemokine network by encoding homologs of chemokines and chemokine receptors and secreted proteins that bind chemokines (1–3). These mechanisms have been identified in large DNA viruses such as herpesviruses and poxviruses. The exceptions are the chemokinel ...
Chemokines regulate a wide array of physiological and pathological processes, including physiological trafficking, inflammation, hematopoiesis, angiogenesis, tumor growth, and human immunodeficiency virus (HIV) infection (1,2). All of these functions are mediated by si ...
With the development of antigen-specific T-cell-receptor (TcR) and B-cell-receptor (BcR) transgenic (Tg) mice, it is now feasible to track single, antigen-specific lymphocyte populations throughout the course of an immune response. Adoptive transfer of the transgenic cell popul ...
Leukocyte recruitment is a hallmark feature of the inflammatory response, which involves a sequential series of molecular interaction between the leukocyte and endothelial cells. First, leukocytes in the mainstream of blood flow come into contact with the endothelium and they roll a ...
Staphylococcal exotoxins (SE) are among the most common etiological agents that cause toxic shock (1). Similar to other superantigens, SE activates T cells polyclonally by binding simultaneously to specific Vβ regions of T-cell receptors (TCR) on T cells and the major histocompatibili ...
The bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and the distantly related staphylococcal enterotoxin A and B (SEA and SEB) are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning, autoimmune diseases, and toxic sh ...
The use of antibodies to selectively destroy tumors has attracted attention since Paul Ehrlich’s dream about “magic bullets,” and it gained support from the demonstration by Pressman in the 1950s that antibodies can be employed to deliver radioisotopes to tumors in rodents. The promise of th ...
Cell-specific cytotoxic heteroconjugates are made by linking bacterial toxins (e.g., diphtheria toxin, Pseudomonas exotoxin A) or plant toxins (e.g., ricin, abrin) to monoclonal antibody (MAb)/ligands that bind target antigens or receptors at the cell surface (1-3). Toxins used for the s ...
Acute myeloid leukemia (AML) has an annual incidence of 2.4 cases per 100,000 persons and is the most common form of acute leukemia in adults (1, 2). AML is a model for drug-resistant human cancers, and current therapies for AML possess a narrow therapeutic margin. The use of high-dose and intensive chemot ...
Immunotoxins (IT) constructed by conventional chemical means using heterobifunctional crosslinking reagents such as
Ribosome-inactivating proteins (RIPs, 1) are plant enzymes that damage ribosomes in an irreversible manner. They can be divided into type 1 RIPs, which are single-chain proteins, and type 2 RIPs, which are heterodimeric proteins consisting of an enzymatically active A-chain connected by a ...