Secretory Leukocyte Protease Inhibitor (SLPI)

Table of Contents:

1. Function

2. Description

3.Gene Structure

4. Role in Disease

Function - SLPI encodes a secreted inhibitor that protects epithelial tissues from serine proteases.  This inhibition contributes to the immune response by protecting epithelial surfaces from attack by endogenous proteolytic enzymes.  It is also thought to have anti-biotic activity and wound repair (O'neil et al 2006). SLPI is an anti-protease and anti-microbial molecule with a role in innate immune defence. Their role is likely to include regulation of protease activity, wound healing and tissue remodelling.

Description - SLPI is an acid-stable polypeptide of molecular weight 12,000, found in seminal fluid, bronchial mucus, and cervical mucus (O'neil et al 2006).

Gene Structure - SLPI consists of 2 exons with an intervening sequence in between the two spanning to approximately 2.6 kbp.  It is flanked by 11 basepair direct repeats; this suggests that the intron may be transposed by some type of event occurring (O'neil et al 2006).  SLPI is a cysteine-rich, 107-amino acid, single-chain polypeptide (Doumas et al 2005). 

 Role in diseases - SLPI's main function is to protect local tissue against the complications of inflammation (Doumas et al 2005). Many diseases, such as emphysema, cystic fibrosis, and idiopathic pulmonary fibrosis, are characterized by increased levels of neutrophil elastase. SLPI is one of the major defenses against the destruction of pulmonary tissues and epithelial tissues by neutrophil elastase. SLPI is considered to be the predominant elastase inhibitor in secretions. Several diseases, including those listed, are actually the result of SLPI and α1-antitrypsin defenses being overwhelmed by neutrophil elastase. It has been suggested that recombinant human SLPI be administered to treat symptoms of cystic fibrosis, genetic emphysema, pneumonia, and asthma.  

• Herpes Simplex Virus- in a recent study SLPI proved to inhibit Herpes Simplex Virus (HSV) infection invitro.  In this experiment, SLPI bound to epithelial cell surfaces which ultimately prevented virus infection.  SLPI acts as protecting agent.  
• Tonsils- In an August issue of The American Journal of Pathology, Researcher, led by Dr. Sharon M. Wahl, PhD, of the National Institute of Dental and Craniofacial Research, brought about the question of whether tonsils could be a transmission site for the spread of HIV.  The tonsils are known to possess a high level of immune cells which may be an easy target to HIV. Scientists also found that there is an abundance of HIV coreceptor CXCR4 protein in the tonsils along with other molecules that bind and capture HIV.  These high levels insinuate which later was proven true that there exists lower levels of SLPI in the tonsils.  This does in fact make it a more susceptible and vulnerable to the transmission of HIV and other foreign invaders.   

• SLPI is an endogenous mucosa associated protein that is proposed to possess anti-human inmmunodeficiency virus type 1 (HIV-1) activity (O'neil et al 2006). It appears that SLPI has the ability to block HIV_1 entry through interaction with a non-CD4 cellular receptor protein.It has been observed that breast milk may be a contributing factor in preventing  HIV-1.  In a study of 122 breast-fed infants born to HIV-1 infected mothers, uninfected infants at 1 month of age possessed higher salivary SLPI levels than those infected with HIV-1. Similarly, Wahl et al. depicted infered that colostrum may also contribute to reducing rates of HIV-1 transmission; due to its higher than breast milk SLPI and anti-HIV-1 nature.